Association of histone modification patterns with transcription factor binding revealed by systematic analysis

Abstract

Selective binding of transcription factors (TFs) to cis-regulatory elements plays an important role in cell-type specific gene expression in mammalian cells. This process is potentially guided by epigenetic states of the chromatin. Recent studies provide large amounts of genome-wide ChlP-seq data for both TF binding and histone modification loci, enabling large-scale analysis of spatial and regulatory interplay between TFs and epigenetic marks. In this paper, the authors report an integrative analysis of multiple public ChlP-seq and RNA-seq data sets, concerning 85 TFs, 9 histone modifications and 5 cell lines, to investigate the genome-wide localization correlations between transcription factor binding sites (TFBSs), histone modification patterns and transcription in human. This study reveals that genome-wide co-localization with histone modifications follow the same pattern for different TFs, and active histone marks typically adjoin TFBSs at a distance around 500 bp. TF occupancy at conserved sequences is found positively correlated with levels and bimodal pattern of active histone marks, and the bimodal and co-localized patterns track with higher gene expression. The correlation among histone modification patterns, TF occupancy and gene transcription suggests the existence of a possible regulatory mechanism that cells may implement to regulate transcription.